- Email: [email protected]
Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study
ARTICLE IN PRESS
Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study Zachary Bulwa, MD,* Victor J. Del Brutto, MD,† Andrea Loggini, MD,* Faten El Ammar, MD,* Raisa C. Martinez, MD,‡ Gregory Christoforidis, MD,§ James R. Brorson, MD,* Agnieszka A. Ardelt, MD, MBA,{ and Fernando D. Goldenberg, MD*
Background and Aim: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. Methods: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. Results: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. Conclusions: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with communityonset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes. Key Words: Acute ischemic stroke—in-hospital stroke—large vessel occlusion— thrombectomy © 2020 Elsevier Inc. All rights reserved.
Background and Aim Acute ischemic stroke (AIS) occurring in patients hospitalized for alternative reasons represent 2%-17% of all strokes.1 In-hospital AIS is associated with worse
outcomes compared to those presenting from the community due to lower rates of intravenous thrombolysis administration in addition to various medical comorbidities.1-3
From the *University of Chicago Medical Center, Department of Neurology, Chicago, Illinois; †University of Miami Health System, Department of Neurology, Miami, Florida; ‡WellStar Kennestone Hospital, Department of Neurology, Marietta, Georgia; §University of Chicago Medical Center, Department of Radiology, Chicago, Illinois; and {MetroHealth Medical Center, Department of Neurological Surgery, Cleveland, Ohio. Received May 29, 2019; revision received January 12, 2020; accepted January 23, 2020. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The Institutional Review Board at the University of Chicago approved the protocol (IRB-17-1593). Address correspondence to Zachary Bulwa, MD, University of Chicago Medical Center, Department of Neurology, 5841 South Maryland Avenue, Chicago, IL, 60637. E-mail: [email protected]. 1052-3057/$ - see front matter © 2020 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104692
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, No. && (&&), 2020: 104692
1
ARTICLE IN PRESS Z. BULWA ET AL.
2
Cardioembolism is a common etiology in this subgroup of patients, often associated with the decompensation of an underlying cardiac disorder, withdrawal of anticoagulant therapy or perioperative complications.1 Cardioembolic strokes have a propensity for intracranial large vessel occlusion (ILVO).4 Inpatients with active malignancy represent another at-risk population for in-hospital AIS due to acquired coagulopathies promoting cerebral embolism.1,5 Mechanical thrombectomy is an established therapy to improve outcomes in patients with AIS due to ILVO.6 Little is known about the incidence of acute ILVO in already hospitalized patients and the feasibility and safety of mechanical thrombectomy in this population. We aimed to identify a cohort of patients with in-hospital AIS due to ILVO and report acute interventions and outcomes.
Methods From September 2012 to December 2018, we retrospectively reviewed all stroke alert cases presenting to a single tertiary care university hospital. From the initiation of our study until late 2013 our institution was an accredited primary stroke center and has since maintained accreditation as a comprehensive stroke center via the Joint Commission. Mechanical thrombectomy was already offered at our institution at the initiation of our study.7 Patient demographics, past medical history, presenting National Institutes of Health Stroke Scale (NIHSS), therapeutic interventions, final diagnosis, and discharge destination were obtained through electronic chart review from our university database.7 Stroke etiology was classified using TOAST criteria,8 with the addition of a perioperative category. Perioperative stroke was considered the definitive etiology in patients undergoing an endovascular or open surgical procedure where ischemic stroke was noted intraprocedurally or within the first 24 hours postprocedurally. This designation does not include ischemic stroke secondary to postoperative atrial fibrillation or myocardial infarction, but rather from suspected arterial emboli dislodged during surgery. Initial vessel imaging (computed tomography [CT] angiography, magnetic resonance angiography, or digital subtraction angiography) at the time of the stroke alert for all inhospital AIS patients was reviewed for the presence of ILVO. ILVO was defined as occlusion of the intracranial internal carotid artery, middle cerebral artery (MCA M1 and proximal M2 segments), or basilar artery. In patients with ILVO, Alberta stroke program early computed tomography score (ASPECTS) was reported from the initial head CT imaging.9 Procedural notes and radiographic images from mechanical thrombectomy cases were reviewed. Stent retrievers (TrevoTM (Stryker Neurovascular), SolitaireTM (Medtronic Neurovascular)) were used in 37 cases. Thirty-five cases were performed using “solumbra” technique.10 A direct aspiration first pass thrombectomy technique was used in 4 cases (Penumbra aspiration catheter, Penumbra, Inc.).10 One patient
was not successfully catheterized in the neurointerventional suite despite multiple attempts. Modified treatment in cerebral ischemia grade was acquired from the procedural note and confirmed by reviewing the accompanying angiography. Successful reperfusion was considered Modified treatment in cerebral ischemia greater than or equal to 2b.11 Feasibility and safety of mechanical thrombectomy was assessed via a case-control study. Inpatients who underwent thrombectomy for acute ILVO (in-hospital group) were matched (1:2) with patients from our own database with acute ILVO presenting from the community (community-onset group). Patients were paired successively on 3 parameters: occlusion site, initial NIHSS, and age, as previously described.12 The authors were blinded to all other demographics, reperfusion results, periprocedural complications, and clinical outcomes of both groups at the time of pairing. Technical feasibility of thrombectomy was assessed by number of passes of thrombectomy device and final reperfusion grade.11 Safety of thrombectomy was assessed either through review of procedural notes and angiographic images (vessel perforation, embolism to new territory) or by postprocedural head imaging (hemorrhagic transformation). Parenchymal hemorrhage was classified on a radiographic spectrum as type 1 or type 2 as previously described.13 In-hospital mortality was also considered as a critical safety variable. Discharge destination was used as a surrogate of clinical outcome. Good outcome was defined as discharge home or to an acute rehabilitation facility. At our institution, a prerequisite for discharge to an acute rehabilitation facility is the ability for the patient to participate in at least 3 hours of rehabilitation daily. Poor outcome was defined as discharge to a subacute rehabilitation or nursing facility, long term acute care hospital, a declaration of hospice, or in-hospital death.14-17 Continuous variables were reported as a median with an interquartile range (IQR). Categorical variables were reported as proportions. Differences in continuous variables were assessed with the Mann-Whitney U test assuming unequal sample variances. Differences between proportions were assessed with the Fisher’s exact test. All significance tests were 2 sided. Differences were considered statistically significant at P less than .05. The Institutional Review Board at our university approved the protocol (IRB-17-1593).
Results From 4515 acute stroke alerts, there were a total of 1460 in-hospital alerts (32%). Of the total in-hospital stroke alerts, 11% were given a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS were candidates for emergent intracranial vessel imaging (61%) and were included in our cohort (Fig 1). Sixty-five patients with inhospital stroke were not candidates for emergent vessel imaging due to hemodynamic instability at the time of the stroke diagnosis requiring immediate cardiopulmonary
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE
Figure 1. Flow chart for patient selection.
support (the majority), demonstrable infarct on head CT matching the clinical syndrome, low initial NIHSS, and time restrictions for endovascular intervention.
3
Table 1 illustrates age, gender, past medical history, initial NIHSS, stroke etiologies, and treatments in patients with AIS who underwent emergent vessel imaging. The groups are separated by those patients with evidence of ILVO and those without ILVO (non-ILVO group). ILVO was identified in 27 patients (26% of patients within this cohort). Inpatients with ILVO were younger than those in the non-ILVO group (57 [IQR 47-68] versus 67 [IQR 59-74], P = .004) and had more severe neurologic deficit on presentation (NIHSS 14 [IQR 7-19] versus 9 [IQR 3-15], P = .031). There were no other statistically significant differences in gender, past medical history, or stroke etiology between inpatients presenting with or without ILVO. Cardioembolism was the responsible etiology for a significant proportion of AIS due to ILVO (48%). Of the 102 inpatients with emergent vessel imaging, only 6 patients were administered tissue plasminogen activator (tPA) despite 69% of activations within this cohort occurring within 4.5 hours of onset (n = 74). Major contraindications to tPA excluding time restrictions included acute bleeding diathesis (n = 19), recent major surgery (n = 18), minor or resolving symptoms (n = 13), amongst a variety of others (Supplemental Table 1). Amongst the ILVO group, 78% of alerts were activated within 6 hours of last known well (n = 21) and 93% were activated within 24 hours of last known well (n = 25). Excluding a case of intraprocedural M2 occlusion (which did not have CT imaging) and a case of basilar artery occlusion, 23 of 25 patients with ILVO had ASPECTS greater than or equal to 6 on initial head CT. ILVO primarily occurred in the MCA M1 segment (n = 14). There were 6 cases of intracranial internal carotid artery (ICA)
Table 1. ILVO and non-ILVO group characteristics ILVO (n = 27) Age (IQR) Female (%) Past medical history (%) Hypertension Hyperlipidemia Diabetes mellitus Atrial fibrillation Congestive heart failure Active cancer NIHSS (IQR) Etiology (%) Large artery atherosclerosis Cardioembolism Small vessel disease Other determined etiology Undetermined etiology Perioperative Reperfusion therapy (%) IV-tPA Mechanical thrombectomy
non-ILVO (n = 75)
P value
57 18
(47-68) (67%)
67 42
(59-74) (56%)
.004 .370
15 7 9 5 12 7 14
(56%) (26%) (33%) (19%) (44%) (26%) (7-19)
56 24 30 16 25 17 9
(75%) (32%) (40%) (21%) (33%) (23%) (3-15)
.087 .632 .647 1.000 .354 .793 .031
2 13 0 6 1 5
(7%) (48%) (0%) (22%) (4%) (19%)
9 20 3 7 8 28
(12%) (27%) (4%) (9%) (11%) (37%)
.086
3 14
(11%) (52%)
3
(4%)
.188
Abbreviations: ILVO, intracranial large vessel occlusion; IQR, interquartile range; IV-tPA, intravenous tissue plasminogen activator; NIHSS, National Institutes of Health Stroke Scale.
ARTICLE IN PRESS Z. BULWA ET AL.
4
occlusion, 6 cases of MCA M2 segment occlusion, and 1 case of basilar artery occlusion in the cohort. Of the 27 inpatients with evidence of ILVO, 14 underwent mechanical thrombectomy (in-hospital group). Thirteen patients with in-hospital AIS with ILVO did not undergo thrombectomy. They were not considered suitable candidates for thrombectomy due to low NIHSS (n = 2), low ASPECTS on initial head CT (n = 3), lack of significant penumbral tissue in stroke of more than 6 hours (n = 3), Moyamoya syndrome (n = 2), recent ischemic stroke (n = 1), and rapidly improving symptoms with robust collateralization on CT angiography (n = 2). Of the 13 inpatients with ILVO who did not undergo thrombectomy, 7 had poor outcomes including 3 deaths during hospitalization (Supplemental Fig 1) The 14 inpatients who underwent thrombectomy were paired with 28 patients presenting from the community with AIS due to acute ILVO (community-onset group) (Supplemental Table 2). The case-control study is depicted in Table 2. Occlusion site was matched between the 2 groups: intracranial ICA occlusion (14%), MCA M1 segment occlusion (57%), MCA M2 segment occlusion (21%), and basilar artery occlusion (7%). NIHSS was equivalent between the in-hospital and community-onset groups (15 [IQR 8-19] versus 15 [IQR 11-18], P = .900). There were no statistically significant differences in age, gender, past medical history, or proportion receiving bridging intravenous tissue plasminogen activator. Stroke etiology was significantly different between the 2 matched groups due to perioperative stroke. There were no statistically significant differences in delays in recognition (time from symptom onset to activation) or in initiating treatment (time from activation to puncture) between the 2 groups (Table 2). Stent retrievers, with the Solumbra technique, were employed in the majority of the cases. There was no difference in the number of passes between the groups. Successful reperfusion was achieved in 86% of patients in the inhospital group and 82% of patients in the community-onset group (P = 1). There were few periprocedural complications overall with no difference amongst the groups, nor did in-hospital mortality differ significantly between the 2 groups. Good outcome was achieved in 79% of patients in the in-hospital group and 61% of patients in the community-onset group (P = 0.313) (Supplemental Fig 2).
Discussion The major findings from our study are the incidence of acute ILVO in hospitalized patients who experience AIS and the feasibility, safety, and clinical outcome of mechanical thrombectomy in this population. In-hospital strokes represents a substantial proportion of all ischemic strokes at our university.7 Nevertheless, these inpatients rarely receive intravenous thrombolysis. Of 167 inpatients with a final diagnosis of AIS from September 2012 to December 2018, only 12 patients received tPA (and
only 6 patients within our emergent vessel imaging cohort of 102 patients). This finding is consistent with previous literature citing delays in recognition as well as the numerous medical comorbidities and heightened bleeding risks that contribute to less tPA administration in hospitalized patients who experience AIS.2-3 Accordingly, we reviewed our stroke alert database to identify a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular reperfusion therapies. To our knowledge this is the first study to determine the incidence of ILVO in a large inpatient stroke database. Of the 102 patients included in our cohort, 26% had angiographic evidence of acute ILVO (n = 27). While difficult to estimate the incidence of ILVO in the inpatients with AIS who were not candidates for emergent vessel imaging, the proportion of ILVO in our emergent vessel imaging cohort is comparable to the reported incidence of communityonset acute ILVO.18-19 This population represents a realword depiction of ILVO in hospitalized patients, as these patients were selected for angiography based on clinical suspicion rather than determined by trial protocol. Inpatients with acute ILVO were younger with more severe neurological deficit at the time of the stroke code activation. There was also a meaningful trend toward more cardioembolism in hospitalized patients with acute ILVO compared to non-ILVO stroke. Cardioembolic strokes have a propensity for ILVO and in the inpatient AIS population may be the result of decompensation of an underlying cardiac disorder or withdrawal of anticoagulant therapy.1,4 The frequent contraindications to IV thrombolysis in hospitalized patients renders thrombectomy the only viable option to achieve reperfusion in appropriate candidates, ie, inpatients with acute ILVO.12 There is limited data on the use of mechanical thrombectomy in already hospitalized patients despite the widespread implementation of in-hospital stroke protocols. A previous study found worse outcomes in hospitalized patients with AIS receiving thrombolytic therapy compared to patients with AIS presenting from the community, including 29 patients (45%) who received thrombectomy. Our case-control study has demonstrated the contrary.20 First, mechanical thrombectomy appears organizationally feasible in this population due to the accessibility of the stroke neurology and neurointerventional teams to inpatients. Previous studies have reported delays in in-hospital AIS recognition and treatment and our data demonstrated a nonstatistically significant doubling of the time from symptom onset to stroke code activation in in-hospital strokes compared to those presenting from the community.3,7,21-23 However, our university protocol prioritizes early recognition by encouraging any health care personnel to activate a stroke code for new onset neurologic signs and as a result, the 93 minute in-hospital delay from symptom onset to activation is the shortest in the literature. Mechanical thrombectomy is also technically feasible in hospitalized patients, as evidenced by the successful reperfusion grades within our in-hospital cohort relative
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE
5
Table 2. Case-control study In-hospital group (n = 14) Age (IQR) Female (%) Past medical history (%) Hypertension Hyperlipidemia Diabetes mellitus Atrial fibrillation Congestive heart failure Active cancer NIHSS (IQR) Etiology (%) Large artery atherosclerosis Cardioembolism Small vessel disease Other determined etiology Undetermined etiology Perioperative Time to treatment (minutes; IQR) Time from onset to activation* Time from activation to puncture Time from onset to puncture* Reperfusion therapy (%) IV-tPA Stent retrievery Solumbra techniquey ADAPT techniquey Passesy (IQR) Post-thrombectomy mTICI 2b/3 Safety Outcomes (%) Parenchymal hematoma type 1 Parenchymal hematoma type 2 Vessel perforation Embolism to new territory In-hospital mortality Discharge Destination (%) Good outcome Home Acute rehabilitation Poor outcome Subacute facility or LTACH Hospice or death
Community-onset group (n = 28)
P value
58 11
(48-69) (79%)
68 18
(57-78) (64%)
.061 .485
9 5 3 2 6 4 15
(64%) (36%) (21%) (14%) (43%) (29%) (8-19)
22 6 8 10 7 2 15
(79%) (21%) (29%) (36%) (25%) (7%) (11-18)
.459 .459 .723 .277 .298 .155 .900
1 6 0 3 0 4
(7%) (43%) (0%) (21%) (0%) (29%)
5 13 0 4 6 0
(18%) (46%) (0%) (14%) (21%) (0%)
.015
93 160 248
(34-161) (77-215) (157-370)
46 146 209
(35-83) (113-195) (172-326)
.406 .660 .920
3 12 11 2 2 12
(21%) (86%) (92%) (14%) (1-3) (86%)
13 25 24 2 3 23
(46%) (93%) (96%) (7%) (2-3) (82%)
.180 .596 1.000 .596 .200 1.000
1 2 2 0 1
(7%) (14%) (14%) (0%) (7%)
2 2 1 0 3
(7%) (7%) (4%) (0%) (11%)
1.000 .590 .254 1.000 1.000
11 4 7 3 1 2
79% 29% 50% 21% 7% 14%
17 4 13 11 5 6
61% 14% 46% 39% 18% 21%
.313
Abbreviations: ADAPT, A direct aspiration first pass thrombectomy; IQR, interquartile range; IV-tPA, intravenous tissue plasminogen activator; LTACH, long-term acute care hospital;.mTICI, Modified treatment in cerebral ischemia; NIHSS, National Institutes of Health Stroke Scale. *n = 25 for community-onset group; defined as the difference in time of known symptom onset to stroke code activation, 3 patients had unknown time of symptom onset. † One patient in the community-onset group was not successfully catheterized (n = 27 for thrombectomy technique).
to the community-onset group. The safety of mechanical thrombectomy was confirmed in the in-hospital group as there were few adverse periprocedural safety consequences, not significantly different from those patients presenting from the community. Last, mechanical thrombectomy demonstrated substantial benefit in suitable candidates, whereas those who did not undergo thrombectomy had poor outcomes including several in-hospital deaths.
This study has several limitations. The retrospective nature of our data collection limits the ability to correct for unforeseen variables. At the time of the study there was not a standardized vessel imaging protocol for inhospital AIS, thus emergent vessel imaging was guided by clinical assessment. Due to an absence of systematic postprocedural NIHSS reporting, we were unable to assess for clinical significance of post-thrombectomy
ARTICLE IN PRESS Z. BULWA ET AL.
6
hemorrhage.24 Additionally, our data is restricted to a single tertiary care university hospital and may not be generalizable to noncomprehensive stroke centers.
Conclusions ILVO is a relatively common finding in patients who develop an AIS while being hospitalized for another reason. Our study demonstrates that the incidence of acute ILVO in this group of patients (26%) is similar to the reported incidence in patients presenting from the community.18-19 Mechanical thrombectomy appears feasible, safe and often, the most viable acute method for reperfusion in hospitalized patients presenting with AIS due to ILVO. AIS due to ILVO is associated with significant morbidity and mortality, however, inpatients with AIS due to ILVO can achieve good outcomes with urgent reperfusion.25-28 Our results clearly suggest the importance of urgent recognition of in-hospital AIS and that endovascular treatment can be offered to appropriate candidates. Hence, there is a need for further studies to optimize strategies for timely recognition of in-hospital AIS and, more specifically, to identify patients harboring acute ILVO who may benefit from acute endovascular intervention.
Conflict of Interest No author has any competing interests or disclosures.
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.jstrokecere brovasdis.2020.104692.
References 1. Cumbler E. In-hospital ischemic stroke. Neurohospitalist 2015;5:173-181. 2. Cumbler E, Wald H, Bhatt DL, et al. Quality of care and outcomes for in-hospital ischemic stroke: findings from the National Get With the Guidelines—Stroke. Stroke 2014;45:231-238. 3. Saltman AP, Silver FL, Fang J, et al. Care and outcomes of patients with in-hospital stroke. JAMA Neurol 2015;72: 749-755. 4. O’Carroll CB, Barrett KM. Cardioembolic stroke. Continuum (Minneap Minn) 2017;23:111-132. 5. Jung S, Jung C, Hyoung K, et al. Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke. Interv Neuroradiol 2018;24:520-528. 6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. 7. Del Brutto VJ, Ardelt A, Loggini A, et al. Clinical characteristics and emergent therapeutic interventions in patients evaluated through the in-hospital stroke alert protocol. J Stroke Cerebrovasc Dis 2019;28:1362-1370.
8. Adams HP Jr., Bendixen BH, Kappelle J, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial Stroke. 1993;24:35-41. 9. Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta stroke program early CT score (ASPECTS) for assessing CT scans in patients with acute ischemic stroke. AJNR Am J Neuroradiol 2001;22:1534-1542. 10. Delgado Almandoz JE, Kayan Y, Young ML, et al. Comparison of clinical outcomes in patients with acute ischemic strokes treated with mechanical thrombectomy using either Solumbra or ADAPT techniques. J Neurointerv Surg 2016;8:1123-1128. 11. Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;44:2650-2663. 12. Premat K, Clovet O, Frasca Polara G, et al. Mechanical thrombectomy in perioperative strokes: a case-control study. Stroke 2017;48:3149-3151. 13. Fiorelli M, Bastianello S, von Kummer R, et al. Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Stroke 1999;30:2280-2284. 14. Zhang Q, Yang Y, Saver JL. Discharge destination after acute hospitalization strongly predicts three month disability outcome in ischemic stroke. Restor Neurol Neurosci 2015;33:771-775. 15. Qureshi AI, Chaudhry SA, Sapkota BL, et al. Discharge destination as a surrogate for modified rankin scale defined outcomes at 3- and 12-months poststroke among stroke survivors. Arch Phys Med Rehabil 2012;93:1408-1413. 16. Belagaje SR, Zander K, Thackeray L, et al. Disposition to home or acute rehabilitation is associated with a favorable clinical outcome in the SENTIS trial. J NeuroIntervent Surg 2015;7:322-325. 17. Belagaje SR, Sun C-HJ, Nogueira RG. Discharge disposition to skilled nursing facility after endovascular reperfusion therapy predicts a poor prognosis. J NeuroIntervent Surg 2015;7:99-103. 18. Lakomkin N, Dhamoon M, Carroll K, et al. Prevalence of large vessel occlusion in patients presenting with acute ischemic stroke: a 10-year systematic review of the literature. J NeuroIntervent Surg 2018;11:241-245. 19. Dozois A, Hampton L, Kingston CW, et al. PLUMBER Study (Prevalence of large vessel occlusion strokes in Mecklenburg county emergency response). Stroke 2017;48:3397-3399. 20. Caparros F, Ferrigno M, Decourcelle A, et al. In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy. J Neurol 2017;264:1804-1810. 21. Alberts M, Brass L, Perry A, et al. Evaluation times for patients with in-hospital strokes. Stroke 1993;24:18171822. 22. Masjuan J, Simal P, Fuentes B, et al. In-hospital stroke treated with intravenous tissue plasminogen activator. Stroke 2008;39:2614-2616. Pubmed ID: 18635852. 23. Vera R, Lago A, Fuentes B, et al. In-hospital stroke: a multi-centre prospective registry. Eur J Neurol 2011;18: 170-176. 24. Larrue V, von Kummer RR, Muller A, et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke 2001;32: 438-441.
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE 25. Smith WS, Tsao JW, Billings ME, et al. Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia. Neurocrit Care 2006;4:14-17. 26. Smith WS, Lev MH, English JD, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke 2009;40:3834-3840.
7 27. Lima FO, Furie KL, Silva GS, et al. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol 2014;71:151-157. 28. Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front Neurol 2017;8:651.
Mechanical Thrombectomy for Patients with In-Hospital Ischemic Stroke: A Case-Control Study Zachary Bulwa, MD,* Victor J. Del Brutto, MD,† Andrea Loggini, MD,* Faten El Ammar, MD,* Raisa C. Martinez, MD,‡ Gregory Christoforidis, MD,§ James R. Brorson, MD,* Agnieszka A. Ardelt, MD, MBA,{ and Fernando D. Goldenberg, MD*
Background and Aim: Patients with in-hospital acute ischemic stroke (AIS) have, in general, worse outcomes compared to those presenting from the community, partly attributed to the numerous contraindications to intravenous thrombolysis. We aimed to identify and analyze a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular therapies. Methods: A retrospective 6-year data analysis was conducted in patients evaluated through the in-hospital stroke alert protocol in a single tertiary care university hospital to identify those with in-hospital AIS due to acute intracranial large vessel occlusion (ILVO). Feasibility and safety of mechanical thrombectomy for in-hospital AIS was assessed in a case-control study comparing inpatients to those presenting from the community. Results: From 1460 in-hospital stroke alert activations, 11% had a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS had emergent intracranial vessel imaging and were included in our cohort. Acute ILVO was identified in 27 patients within this cohort. Patients were younger in the ILVO group and had more severe neurologic deficit on presentation. Compared to a matched (1:2) control group of patients presenting from the community, inpatients who underwent mechanical thrombectomy achieved equivalent technical success, safety, and clinical outcomes. Conclusions: The incidence of acute ILVO in patients with in-hospital AIS who underwent emergent vessel imaging is similar to the reported incidence of ILVO in patients presenting with communityonset AIS. Among patients with in-hospital AIS secondary to ILVO, mechanical thrombectomy is a feasible and safe therapy associated with favorable outcomes. Key Words: Acute ischemic stroke—in-hospital stroke—large vessel occlusion— thrombectomy © 2020 Elsevier Inc. All rights reserved.
Background and Aim Acute ischemic stroke (AIS) occurring in patients hospitalized for alternative reasons represent 2%-17% of all strokes.1 In-hospital AIS is associated with worse
outcomes compared to those presenting from the community due to lower rates of intravenous thrombolysis administration in addition to various medical comorbidities.1-3
From the *University of Chicago Medical Center, Department of Neurology, Chicago, Illinois; †University of Miami Health System, Department of Neurology, Miami, Florida; ‡WellStar Kennestone Hospital, Department of Neurology, Marietta, Georgia; §University of Chicago Medical Center, Department of Radiology, Chicago, Illinois; and {MetroHealth Medical Center, Department of Neurological Surgery, Cleveland, Ohio. Received May 29, 2019; revision received January 12, 2020; accepted January 23, 2020. Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The Institutional Review Board at the University of Chicago approved the protocol (IRB-17-1593). Address correspondence to Zachary Bulwa, MD, University of Chicago Medical Center, Department of Neurology, 5841 South Maryland Avenue, Chicago, IL, 60637. E-mail: [email protected]. 1052-3057/$ - see front matter © 2020 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104692
Journal of Stroke and Cerebrovascular Diseases, Vol. &&, No. && (&&), 2020: 104692
1
ARTICLE IN PRESS Z. BULWA ET AL.
2
Cardioembolism is a common etiology in this subgroup of patients, often associated with the decompensation of an underlying cardiac disorder, withdrawal of anticoagulant therapy or perioperative complications.1 Cardioembolic strokes have a propensity for intracranial large vessel occlusion (ILVO).4 Inpatients with active malignancy represent another at-risk population for in-hospital AIS due to acquired coagulopathies promoting cerebral embolism.1,5 Mechanical thrombectomy is an established therapy to improve outcomes in patients with AIS due to ILVO.6 Little is known about the incidence of acute ILVO in already hospitalized patients and the feasibility and safety of mechanical thrombectomy in this population. We aimed to identify a cohort of patients with in-hospital AIS due to ILVO and report acute interventions and outcomes.
Methods From September 2012 to December 2018, we retrospectively reviewed all stroke alert cases presenting to a single tertiary care university hospital. From the initiation of our study until late 2013 our institution was an accredited primary stroke center and has since maintained accreditation as a comprehensive stroke center via the Joint Commission. Mechanical thrombectomy was already offered at our institution at the initiation of our study.7 Patient demographics, past medical history, presenting National Institutes of Health Stroke Scale (NIHSS), therapeutic interventions, final diagnosis, and discharge destination were obtained through electronic chart review from our university database.7 Stroke etiology was classified using TOAST criteria,8 with the addition of a perioperative category. Perioperative stroke was considered the definitive etiology in patients undergoing an endovascular or open surgical procedure where ischemic stroke was noted intraprocedurally or within the first 24 hours postprocedurally. This designation does not include ischemic stroke secondary to postoperative atrial fibrillation or myocardial infarction, but rather from suspected arterial emboli dislodged during surgery. Initial vessel imaging (computed tomography [CT] angiography, magnetic resonance angiography, or digital subtraction angiography) at the time of the stroke alert for all inhospital AIS patients was reviewed for the presence of ILVO. ILVO was defined as occlusion of the intracranial internal carotid artery, middle cerebral artery (MCA M1 and proximal M2 segments), or basilar artery. In patients with ILVO, Alberta stroke program early computed tomography score (ASPECTS) was reported from the initial head CT imaging.9 Procedural notes and radiographic images from mechanical thrombectomy cases were reviewed. Stent retrievers (TrevoTM (Stryker Neurovascular), SolitaireTM (Medtronic Neurovascular)) were used in 37 cases. Thirty-five cases were performed using “solumbra” technique.10 A direct aspiration first pass thrombectomy technique was used in 4 cases (Penumbra aspiration catheter, Penumbra, Inc.).10 One patient
was not successfully catheterized in the neurointerventional suite despite multiple attempts. Modified treatment in cerebral ischemia grade was acquired from the procedural note and confirmed by reviewing the accompanying angiography. Successful reperfusion was considered Modified treatment in cerebral ischemia greater than or equal to 2b.11 Feasibility and safety of mechanical thrombectomy was assessed via a case-control study. Inpatients who underwent thrombectomy for acute ILVO (in-hospital group) were matched (1:2) with patients from our own database with acute ILVO presenting from the community (community-onset group). Patients were paired successively on 3 parameters: occlusion site, initial NIHSS, and age, as previously described.12 The authors were blinded to all other demographics, reperfusion results, periprocedural complications, and clinical outcomes of both groups at the time of pairing. Technical feasibility of thrombectomy was assessed by number of passes of thrombectomy device and final reperfusion grade.11 Safety of thrombectomy was assessed either through review of procedural notes and angiographic images (vessel perforation, embolism to new territory) or by postprocedural head imaging (hemorrhagic transformation). Parenchymal hemorrhage was classified on a radiographic spectrum as type 1 or type 2 as previously described.13 In-hospital mortality was also considered as a critical safety variable. Discharge destination was used as a surrogate of clinical outcome. Good outcome was defined as discharge home or to an acute rehabilitation facility. At our institution, a prerequisite for discharge to an acute rehabilitation facility is the ability for the patient to participate in at least 3 hours of rehabilitation daily. Poor outcome was defined as discharge to a subacute rehabilitation or nursing facility, long term acute care hospital, a declaration of hospice, or in-hospital death.14-17 Continuous variables were reported as a median with an interquartile range (IQR). Categorical variables were reported as proportions. Differences in continuous variables were assessed with the Mann-Whitney U test assuming unequal sample variances. Differences between proportions were assessed with the Fisher’s exact test. All significance tests were 2 sided. Differences were considered statistically significant at P less than .05. The Institutional Review Board at our university approved the protocol (IRB-17-1593).
Results From 4515 acute stroke alerts, there were a total of 1460 in-hospital alerts (32%). Of the total in-hospital stroke alerts, 11% were given a final diagnosis of AIS (n = 167). One hundred and two patients with in-hospital AIS were candidates for emergent intracranial vessel imaging (61%) and were included in our cohort (Fig 1). Sixty-five patients with inhospital stroke were not candidates for emergent vessel imaging due to hemodynamic instability at the time of the stroke diagnosis requiring immediate cardiopulmonary
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE
Figure 1. Flow chart for patient selection.
support (the majority), demonstrable infarct on head CT matching the clinical syndrome, low initial NIHSS, and time restrictions for endovascular intervention.
3
Table 1 illustrates age, gender, past medical history, initial NIHSS, stroke etiologies, and treatments in patients with AIS who underwent emergent vessel imaging. The groups are separated by those patients with evidence of ILVO and those without ILVO (non-ILVO group). ILVO was identified in 27 patients (26% of patients within this cohort). Inpatients with ILVO were younger than those in the non-ILVO group (57 [IQR 47-68] versus 67 [IQR 59-74], P = .004) and had more severe neurologic deficit on presentation (NIHSS 14 [IQR 7-19] versus 9 [IQR 3-15], P = .031). There were no other statistically significant differences in gender, past medical history, or stroke etiology between inpatients presenting with or without ILVO. Cardioembolism was the responsible etiology for a significant proportion of AIS due to ILVO (48%). Of the 102 inpatients with emergent vessel imaging, only 6 patients were administered tissue plasminogen activator (tPA) despite 69% of activations within this cohort occurring within 4.5 hours of onset (n = 74). Major contraindications to tPA excluding time restrictions included acute bleeding diathesis (n = 19), recent major surgery (n = 18), minor or resolving symptoms (n = 13), amongst a variety of others (Supplemental Table 1). Amongst the ILVO group, 78% of alerts were activated within 6 hours of last known well (n = 21) and 93% were activated within 24 hours of last known well (n = 25). Excluding a case of intraprocedural M2 occlusion (which did not have CT imaging) and a case of basilar artery occlusion, 23 of 25 patients with ILVO had ASPECTS greater than or equal to 6 on initial head CT. ILVO primarily occurred in the MCA M1 segment (n = 14). There were 6 cases of intracranial internal carotid artery (ICA)
Table 1. ILVO and non-ILVO group characteristics ILVO (n = 27) Age (IQR) Female (%) Past medical history (%) Hypertension Hyperlipidemia Diabetes mellitus Atrial fibrillation Congestive heart failure Active cancer NIHSS (IQR) Etiology (%) Large artery atherosclerosis Cardioembolism Small vessel disease Other determined etiology Undetermined etiology Perioperative Reperfusion therapy (%) IV-tPA Mechanical thrombectomy
non-ILVO (n = 75)
P value
57 18
(47-68) (67%)
67 42
(59-74) (56%)
.004 .370
15 7 9 5 12 7 14
(56%) (26%) (33%) (19%) (44%) (26%) (7-19)
56 24 30 16 25 17 9
(75%) (32%) (40%) (21%) (33%) (23%) (3-15)
.087 .632 .647 1.000 .354 .793 .031
2 13 0 6 1 5
(7%) (48%) (0%) (22%) (4%) (19%)
9 20 3 7 8 28
(12%) (27%) (4%) (9%) (11%) (37%)
.086
3 14
(11%) (52%)
3
(4%)
.188
Abbreviations: ILVO, intracranial large vessel occlusion; IQR, interquartile range; IV-tPA, intravenous tissue plasminogen activator; NIHSS, National Institutes of Health Stroke Scale.
ARTICLE IN PRESS Z. BULWA ET AL.
4
occlusion, 6 cases of MCA M2 segment occlusion, and 1 case of basilar artery occlusion in the cohort. Of the 27 inpatients with evidence of ILVO, 14 underwent mechanical thrombectomy (in-hospital group). Thirteen patients with in-hospital AIS with ILVO did not undergo thrombectomy. They were not considered suitable candidates for thrombectomy due to low NIHSS (n = 2), low ASPECTS on initial head CT (n = 3), lack of significant penumbral tissue in stroke of more than 6 hours (n = 3), Moyamoya syndrome (n = 2), recent ischemic stroke (n = 1), and rapidly improving symptoms with robust collateralization on CT angiography (n = 2). Of the 13 inpatients with ILVO who did not undergo thrombectomy, 7 had poor outcomes including 3 deaths during hospitalization (Supplemental Fig 1) The 14 inpatients who underwent thrombectomy were paired with 28 patients presenting from the community with AIS due to acute ILVO (community-onset group) (Supplemental Table 2). The case-control study is depicted in Table 2. Occlusion site was matched between the 2 groups: intracranial ICA occlusion (14%), MCA M1 segment occlusion (57%), MCA M2 segment occlusion (21%), and basilar artery occlusion (7%). NIHSS was equivalent between the in-hospital and community-onset groups (15 [IQR 8-19] versus 15 [IQR 11-18], P = .900). There were no statistically significant differences in age, gender, past medical history, or proportion receiving bridging intravenous tissue plasminogen activator. Stroke etiology was significantly different between the 2 matched groups due to perioperative stroke. There were no statistically significant differences in delays in recognition (time from symptom onset to activation) or in initiating treatment (time from activation to puncture) between the 2 groups (Table 2). Stent retrievers, with the Solumbra technique, were employed in the majority of the cases. There was no difference in the number of passes between the groups. Successful reperfusion was achieved in 86% of patients in the inhospital group and 82% of patients in the community-onset group (P = 1). There were few periprocedural complications overall with no difference amongst the groups, nor did in-hospital mortality differ significantly between the 2 groups. Good outcome was achieved in 79% of patients in the in-hospital group and 61% of patients in the community-onset group (P = 0.313) (Supplemental Fig 2).
Discussion The major findings from our study are the incidence of acute ILVO in hospitalized patients who experience AIS and the feasibility, safety, and clinical outcome of mechanical thrombectomy in this population. In-hospital strokes represents a substantial proportion of all ischemic strokes at our university.7 Nevertheless, these inpatients rarely receive intravenous thrombolysis. Of 167 inpatients with a final diagnosis of AIS from September 2012 to December 2018, only 12 patients received tPA (and
only 6 patients within our emergent vessel imaging cohort of 102 patients). This finding is consistent with previous literature citing delays in recognition as well as the numerous medical comorbidities and heightened bleeding risks that contribute to less tPA administration in hospitalized patients who experience AIS.2-3 Accordingly, we reviewed our stroke alert database to identify a group of patients with in-hospital AIS who remain suitable candidates for acute endovascular reperfusion therapies. To our knowledge this is the first study to determine the incidence of ILVO in a large inpatient stroke database. Of the 102 patients included in our cohort, 26% had angiographic evidence of acute ILVO (n = 27). While difficult to estimate the incidence of ILVO in the inpatients with AIS who were not candidates for emergent vessel imaging, the proportion of ILVO in our emergent vessel imaging cohort is comparable to the reported incidence of communityonset acute ILVO.18-19 This population represents a realword depiction of ILVO in hospitalized patients, as these patients were selected for angiography based on clinical suspicion rather than determined by trial protocol. Inpatients with acute ILVO were younger with more severe neurological deficit at the time of the stroke code activation. There was also a meaningful trend toward more cardioembolism in hospitalized patients with acute ILVO compared to non-ILVO stroke. Cardioembolic strokes have a propensity for ILVO and in the inpatient AIS population may be the result of decompensation of an underlying cardiac disorder or withdrawal of anticoagulant therapy.1,4 The frequent contraindications to IV thrombolysis in hospitalized patients renders thrombectomy the only viable option to achieve reperfusion in appropriate candidates, ie, inpatients with acute ILVO.12 There is limited data on the use of mechanical thrombectomy in already hospitalized patients despite the widespread implementation of in-hospital stroke protocols. A previous study found worse outcomes in hospitalized patients with AIS receiving thrombolytic therapy compared to patients with AIS presenting from the community, including 29 patients (45%) who received thrombectomy. Our case-control study has demonstrated the contrary.20 First, mechanical thrombectomy appears organizationally feasible in this population due to the accessibility of the stroke neurology and neurointerventional teams to inpatients. Previous studies have reported delays in in-hospital AIS recognition and treatment and our data demonstrated a nonstatistically significant doubling of the time from symptom onset to stroke code activation in in-hospital strokes compared to those presenting from the community.3,7,21-23 However, our university protocol prioritizes early recognition by encouraging any health care personnel to activate a stroke code for new onset neurologic signs and as a result, the 93 minute in-hospital delay from symptom onset to activation is the shortest in the literature. Mechanical thrombectomy is also technically feasible in hospitalized patients, as evidenced by the successful reperfusion grades within our in-hospital cohort relative
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE
5
Table 2. Case-control study In-hospital group (n = 14) Age (IQR) Female (%) Past medical history (%) Hypertension Hyperlipidemia Diabetes mellitus Atrial fibrillation Congestive heart failure Active cancer NIHSS (IQR) Etiology (%) Large artery atherosclerosis Cardioembolism Small vessel disease Other determined etiology Undetermined etiology Perioperative Time to treatment (minutes; IQR) Time from onset to activation* Time from activation to puncture Time from onset to puncture* Reperfusion therapy (%) IV-tPA Stent retrievery Solumbra techniquey ADAPT techniquey Passesy (IQR) Post-thrombectomy mTICI 2b/3 Safety Outcomes (%) Parenchymal hematoma type 1 Parenchymal hematoma type 2 Vessel perforation Embolism to new territory In-hospital mortality Discharge Destination (%) Good outcome Home Acute rehabilitation Poor outcome Subacute facility or LTACH Hospice or death
Community-onset group (n = 28)
P value
58 11
(48-69) (79%)
68 18
(57-78) (64%)
.061 .485
9 5 3 2 6 4 15
(64%) (36%) (21%) (14%) (43%) (29%) (8-19)
22 6 8 10 7 2 15
(79%) (21%) (29%) (36%) (25%) (7%) (11-18)
.459 .459 .723 .277 .298 .155 .900
1 6 0 3 0 4
(7%) (43%) (0%) (21%) (0%) (29%)
5 13 0 4 6 0
(18%) (46%) (0%) (14%) (21%) (0%)
.015
93 160 248
(34-161) (77-215) (157-370)
46 146 209
(35-83) (113-195) (172-326)
.406 .660 .920
3 12 11 2 2 12
(21%) (86%) (92%) (14%) (1-3) (86%)
13 25 24 2 3 23
(46%) (93%) (96%) (7%) (2-3) (82%)
.180 .596 1.000 .596 .200 1.000
1 2 2 0 1
(7%) (14%) (14%) (0%) (7%)
2 2 1 0 3
(7%) (7%) (4%) (0%) (11%)
1.000 .590 .254 1.000 1.000
11 4 7 3 1 2
79% 29% 50% 21% 7% 14%
17 4 13 11 5 6
61% 14% 46% 39% 18% 21%
.313
Abbreviations: ADAPT, A direct aspiration first pass thrombectomy; IQR, interquartile range; IV-tPA, intravenous tissue plasminogen activator; LTACH, long-term acute care hospital;.mTICI, Modified treatment in cerebral ischemia; NIHSS, National Institutes of Health Stroke Scale. *n = 25 for community-onset group; defined as the difference in time of known symptom onset to stroke code activation, 3 patients had unknown time of symptom onset. † One patient in the community-onset group was not successfully catheterized (n = 27 for thrombectomy technique).
to the community-onset group. The safety of mechanical thrombectomy was confirmed in the in-hospital group as there were few adverse periprocedural safety consequences, not significantly different from those patients presenting from the community. Last, mechanical thrombectomy demonstrated substantial benefit in suitable candidates, whereas those who did not undergo thrombectomy had poor outcomes including several in-hospital deaths.
This study has several limitations. The retrospective nature of our data collection limits the ability to correct for unforeseen variables. At the time of the study there was not a standardized vessel imaging protocol for inhospital AIS, thus emergent vessel imaging was guided by clinical assessment. Due to an absence of systematic postprocedural NIHSS reporting, we were unable to assess for clinical significance of post-thrombectomy
ARTICLE IN PRESS Z. BULWA ET AL.
6
hemorrhage.24 Additionally, our data is restricted to a single tertiary care university hospital and may not be generalizable to noncomprehensive stroke centers.
Conclusions ILVO is a relatively common finding in patients who develop an AIS while being hospitalized for another reason. Our study demonstrates that the incidence of acute ILVO in this group of patients (26%) is similar to the reported incidence in patients presenting from the community.18-19 Mechanical thrombectomy appears feasible, safe and often, the most viable acute method for reperfusion in hospitalized patients presenting with AIS due to ILVO. AIS due to ILVO is associated with significant morbidity and mortality, however, inpatients with AIS due to ILVO can achieve good outcomes with urgent reperfusion.25-28 Our results clearly suggest the importance of urgent recognition of in-hospital AIS and that endovascular treatment can be offered to appropriate candidates. Hence, there is a need for further studies to optimize strategies for timely recognition of in-hospital AIS and, more specifically, to identify patients harboring acute ILVO who may benefit from acute endovascular intervention.
Conflict of Interest No author has any competing interests or disclosures.
Supplementary materials Supplementary material associated with this article can be found in the online version at doi:10.1016/j.jstrokecere brovasdis.2020.104692.
References 1. Cumbler E. In-hospital ischemic stroke. Neurohospitalist 2015;5:173-181. 2. Cumbler E, Wald H, Bhatt DL, et al. Quality of care and outcomes for in-hospital ischemic stroke: findings from the National Get With the Guidelines—Stroke. Stroke 2014;45:231-238. 3. Saltman AP, Silver FL, Fang J, et al. Care and outcomes of patients with in-hospital stroke. JAMA Neurol 2015;72: 749-755. 4. O’Carroll CB, Barrett KM. Cardioembolic stroke. Continuum (Minneap Minn) 2017;23:111-132. 5. Jung S, Jung C, Hyoung K, et al. Procedural and clinical outcomes of endovascular recanalization therapy in patients with cancer-related stroke. Interv Neuroradiol 2018;24:520-528. 6. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46-e110. 7. Del Brutto VJ, Ardelt A, Loggini A, et al. Clinical characteristics and emergent therapeutic interventions in patients evaluated through the in-hospital stroke alert protocol. J Stroke Cerebrovasc Dis 2019;28:1362-1370.
8. Adams HP Jr., Bendixen BH, Kappelle J, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial Stroke. 1993;24:35-41. 9. Pexman JH, Barber PA, Hill MD, et al. Use of the Alberta stroke program early CT score (ASPECTS) for assessing CT scans in patients with acute ischemic stroke. AJNR Am J Neuroradiol 2001;22:1534-1542. 10. Delgado Almandoz JE, Kayan Y, Young ML, et al. Comparison of clinical outcomes in patients with acute ischemic strokes treated with mechanical thrombectomy using either Solumbra or ADAPT techniques. J Neurointerv Surg 2016;8:1123-1128. 11. Zaidat OO, Yoo AJ, Khatri P, et al. Recommendations on angiographic revascularization grading standards for acute ischemic stroke: a consensus statement. Stroke 2013;44:2650-2663. 12. Premat K, Clovet O, Frasca Polara G, et al. Mechanical thrombectomy in perioperative strokes: a case-control study. Stroke 2017;48:3149-3151. 13. Fiorelli M, Bastianello S, von Kummer R, et al. Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Stroke 1999;30:2280-2284. 14. Zhang Q, Yang Y, Saver JL. Discharge destination after acute hospitalization strongly predicts three month disability outcome in ischemic stroke. Restor Neurol Neurosci 2015;33:771-775. 15. Qureshi AI, Chaudhry SA, Sapkota BL, et al. Discharge destination as a surrogate for modified rankin scale defined outcomes at 3- and 12-months poststroke among stroke survivors. Arch Phys Med Rehabil 2012;93:1408-1413. 16. Belagaje SR, Zander K, Thackeray L, et al. Disposition to home or acute rehabilitation is associated with a favorable clinical outcome in the SENTIS trial. J NeuroIntervent Surg 2015;7:322-325. 17. Belagaje SR, Sun C-HJ, Nogueira RG. Discharge disposition to skilled nursing facility after endovascular reperfusion therapy predicts a poor prognosis. J NeuroIntervent Surg 2015;7:99-103. 18. Lakomkin N, Dhamoon M, Carroll K, et al. Prevalence of large vessel occlusion in patients presenting with acute ischemic stroke: a 10-year systematic review of the literature. J NeuroIntervent Surg 2018;11:241-245. 19. Dozois A, Hampton L, Kingston CW, et al. PLUMBER Study (Prevalence of large vessel occlusion strokes in Mecklenburg county emergency response). Stroke 2017;48:3397-3399. 20. Caparros F, Ferrigno M, Decourcelle A, et al. In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy. J Neurol 2017;264:1804-1810. 21. Alberts M, Brass L, Perry A, et al. Evaluation times for patients with in-hospital strokes. Stroke 1993;24:18171822. 22. Masjuan J, Simal P, Fuentes B, et al. In-hospital stroke treated with intravenous tissue plasminogen activator. Stroke 2008;39:2614-2616. Pubmed ID: 18635852. 23. Vera R, Lago A, Fuentes B, et al. In-hospital stroke: a multi-centre prospective registry. Eur J Neurol 2011;18: 170-176. 24. Larrue V, von Kummer RR, Muller A, et al. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke 2001;32: 438-441.
ARTICLE IN PRESS THROMBECTOMY IN PATIENTS WITH IN-HOSPITAL STROKE 25. Smith WS, Tsao JW, Billings ME, et al. Prognostic significance of angiographically confirmed large vessel intracranial occlusion in patients presenting with acute brain ischemia. Neurocrit Care 2006;4:14-17. 26. Smith WS, Lev MH, English JD, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke 2009;40:3834-3840.
7 27. Lima FO, Furie KL, Silva GS, et al. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol 2014;71:151-157. 28. Malhotra K, Gornbein J, Saver JL. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death: a review. Front Neurol 2017;8:651.